The interaction of the host immune system with implantable materials has historically been considered to be a negative occurrence associated with downstream encapsulation and/or implant failure; however, it is now increasingly recognized that host-implant interactions can play both positive and negative roles following placement. In particular, macrophages have been described as key mediators of the host-implant interaction and critical determinants of downstream integration and functionality.
The host response to implanted materials begins immediately upon introduction of the material into the host tissue and encompasses multiple overlapping phases including injury, protein adsorption, acute inflammation, chronic inflammation, foreign body reaction, granulation tissue formation and eventual encapsulation (1). It is recognized that the early interactions which occur at the material-tissue interface represent the initiating events which drive subsequent paracrine and autocrine processes of the host response and subsequent tissue remodeling with significant implications for downstream performance. Recently, macrophage-implant interactions in particular have received considerable attention as a primary determinant of the outcome of biomaterials placement (2-7). A spectrum of macrophage phenotypes contained between two extremes has been identified, ranging from pro-inflammatory (M1) to anti-inflammatory/regulatory (M2) phenotypes, with significant implications in disease, tissue remodeling following injury, and biomaterial performance (3, 8-12). Materials which elicit improved or regenerative remodeling outcomes are associated with a shift from an initially M1 to a more M2 profile during the early stages of the inflammatory response which follows implantation (13-19). Therefore, there is a need in the art for implantable biomaterial that directly modulates the early-stage macrophage response against the biomaterial in order to promote downstream tissue integration and functional remodeling in the long-term.